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ErbB Signaling Pathway Regulates The Transdifferentiation Potential Of Reactive Astrocytes In Cortex And Protein Transportation Between Astrocytes And Neurons

Posted on:2020-11-22Degree:MasterType:Thesis
Country:ChinaCandidate:J Y CaoFull Text:PDF
GTID:2404330590983332Subject:Developmental Biology
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Reactive astrocytes are an important pathological feature of neurological diseases and an important target for the study of new therapies for neurological diseases.The ErbB signaling pathway is an important molecular mechanism regulating the reactive responses of astrocytes.Our previous study found that reactive astrocytes induced by ErbB signaling pathway are capable of self-renewal and express neural stem cell markers.Hans-Hermann Gerdes et al.found that astrocytes and neurons have transportation of cytoplasmic substances.We speculated that ErbB signaling pathway may play a regulatory role in transdifferentiation of reactive astrocytes and/or their material exchange with neurons.Therefore,we constructed a conditionally controlled transgenic mouse model to specifically express ErbB2 in astrocytes,and continuously activate ErbB signaling pathway in astrocytes to induce astrocyte activation.By using genetic tracing to track their progeny,and tracer proteins to study their material exchange,our results showed that reactive astrocytes in the prefrontal cortex of adult mice could not transdifferentiate into neurons,but they could transport cytoplasmic proteins to neurons.Upregulation of the ErbB signaling pathway could inhibit this cellular behavior.In summary,our results indicate that ErbB signaling pathway regulates a variety of cellular behaviors after astrocyte activation,including maintenance of stem cell characteristics and inhibition of cell material transportation.These findings provide important experimental evidence for targeting astrocyteimplicated neurological diseases.
Keywords/Search Tags:reactive astrocytes, ErbB2 signaling pathway, transdifferentiation, neurons, Prefrontal cortex, Material tran
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